The TC-83 vaccine strain of Venezuelan Encephalitis virus induces a sustained diminution of glucose-stimulated insulin release from hamsters as long as 3 months following virus inoculation. This insulin release abnormality is associated with a transient abnormality of glucose tolerance. We have developed an in vivo isolated islet preparation technique for perifusion experiments to attempt delineate the mechanism of this virus induced defect in insulin release. Our experiments to date reveal that this abnormality of glucose stimulated insulin release exists in vitro in islet perifused with "high" (20 mM). glucose. There is also a significant diminution of ISMM arginine-stimulated insulin release; but not tolbutamide (1 mM) stimulated insulin release. 1 mM tolbutamide corrects the defect in 20 mM glucose stimulated insulin release in infected islets as does 10 mM theophylline and 1 mM Dibutyryl cyclic AMP. These data suggest that there may be a virus-induced defect at the level of the putative glucose-receptor on the beta cell membrane but that events distal to the cyclic AMP system of the beta cell are intact. Further, in vitro perifusion experiments are ongoing to elucidate the precise mechanism(s) involved.